Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile.
Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
Adv Exp Med Biol. 2023;1408:25-47. doi: 10.1007/978-3-031-26163-3_2.
Hemostasis preserves blood fluidity and prevents its loss after vessel injury. The maintenance of blood fluidity requires a delicate balance between pro-coagulant and fibrinolytic status. Endothelial cells (ECs) in the inner face of blood vessels maintain hemostasis through balancing anti-thrombotic and pro-fibrinolytic activities. Dyslipidemias are linked to hemostatic alterations. Thus, it is necessary a better understanding of the underlying mechanisms linking hemostasis with dyslipidemia. Statins are drugs that decrease cholesterol levels in the blood and are the gold standard for treating hyperlipidemias. Statins can be classified into natural and synthetic molecules, approved for the treatment of hypercholesterolemia. The classical mechanism of action of statins is by competitive inhibition of a key enzyme in the synthesis pathway of cholesterol, the HMG-CoA reductase. Statins are frequently administrated by oral ingestion and its interaction with other drugs and food supplements is associated with altered bioavailability. In this review we deeply discuss the actions of statins beyond the control of dyslipidemias, focusing on the actions in thrombotic modulation, vascular and cardiovascular-related diseases, metabolic diseases including metabolic syndrome, diabetes, hyperlipidemia, and hypertension, and chronic diseases such as cancer, chronic obstructive pulmonary disease, and chronic kidney disease. Furthermore, we were prompted to delved deeper in the molecular mechanisms by means statins regulate coagulation acting on liver, platelets, and endothelium. Clinical evidence show that statins are effective regulators of dyslipidemia with a high impact in hemostasis regulation and its deleterious consequences. However, studies are required to elucidate its underlying molecular mechanism and improving their therapeutical actions.
止血作用可维持血液的流动性并防止血管损伤后的血液流失。维持血液流动性需要在促凝和纤维蛋白溶解状态之间达到精细的平衡。血管内表面的内皮细胞(ECs)通过平衡抗血栓和促纤维蛋白溶解活性来维持止血作用。血脂异常与止血改变有关。因此,有必要更好地了解将止血作用与血脂异常联系起来的潜在机制。他汀类药物是降低血液中胆固醇水平的药物,是治疗高脂血症的金标准。他汀类药物可分为天然和合成分子,被批准用于治疗高胆固醇血症。他汀类药物的经典作用机制是通过竞争性抑制胆固醇合成途径中的关键酶,即羟甲基戊二酰辅酶 A 还原酶。他汀类药物通常通过口服给药,其与其他药物和膳食补充剂的相互作用与生物利用度改变有关。在这篇综述中,我们深入探讨了他汀类药物在控制血脂异常之外的作用,重点讨论了在血栓调节、血管和心血管相关疾病、代谢疾病(包括代谢综合征、糖尿病、高脂血症和高血压)以及慢性疾病(如癌症、慢性阻塞性肺疾病和慢性肾脏病)中的作用。此外,我们深入研究了他汀类药物通过作用于肝脏、血小板和内皮细胞来调节凝血的分子机制。临床证据表明,他汀类药物是调节血脂异常的有效药物,对止血作用的调节及其有害后果有很大影响。然而,仍需要研究来阐明其潜在的分子机制并改善其治疗作用。